ArticleCancer research2011
EGF receptor inhibition radiosensitizes NSCLC cells by inducing senescence in cells sustaining DNA double-strand breaks.
Article in Cancer research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02556593 (IMRT Combined With Erlotinib Compared With Whole-brain Radiotherapy for EGFR Wild Type Non-small Cell Lung Cancer With 4-10 Brain Metastases), which is not on this map. Cited by 60 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
IMRT Combined With Erlotinib Compared With Whole-brain Radiotherapy for EGFR Wild Type Non-small Cell Lung Cancer With 4-10 Brain Metastases
Who cites it
60 citing papers in PubMed, 111 citations in OpenAlex.
- Induction and concurrent aumolertinib with radiotherapy for EGFR-mutated stage III NSCLC: results of phase III ADVANCE trial and real-world validation.Signal transduction and targeted therapy · 2026Trial
- Adding Erlotinib to Chemoradiation Improves Overall Survival but Not Progression-Free Survival in Stage III Non-Small Cell Lung Cancer.International journal of radiation oncology, biology, physics · 2015Trial
- Postoperative chemoradiotherapy and cetuximab for high-risk squamous cell carcinoma of the head and neck: Radiation Therapy Oncology Group RTOG-0234.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2014Trial
- Tumor cells escape from therapy-induced senescence: from molecular mechanisms to targeted intervention.Biology direct · 2026Review
- Programmed Death-Ligand 1 Expression Predicts Poor Prognosis in Patients With Early-Stage Non-Small-Cell Lung Cancer Undergoing Stereotactic Body Radiotherapy.Thoracic cancer · 2026Article
- Disproportionality Analysis of Hematologic Adverse Event Signals Associated with Venetoclax in Combination with Senescence-Inducing Chemotherapy.Journal of clinical medicine · 2026Article
- Cellular senescence in lung cancer immune microenvironment and senotherapeutic opportunities.iScience · 2026Review
- Targeting Senescence in Oncology: An Emerging Therapeutic Avenue for Cancer.Current oncology (Toronto, Ont.) · 2025Review
- CEG-0598, a novel dual inhibitor of EGFR and C5aR demonstrates in vitro anticancer and antimetastatic activity in prostate cancer cells.Discover oncology · 2025Article
- SDC1-TGM2-FLOT1-BHMT complex determines radiosensitivity of glioblastoma by influencing the fusion of autophagosomes with lysosomes.Theranostics · 2023Article
- Critical role of lncEPAT in coupling dysregulated EGFR pathway and histone H2A deubiquitination during glioblastoma tumorigenesis.Science advances · 2022Article
- IL-1 and senescence: Friends and foe of EGFR neutralization and immunotherapy.Frontiers in cell and developmental biology · 2022Review
- Cellular senescence in cancer: from mechanisms to detection.Molecular oncology · 2021Review
- Targeting the DNA replication stress phenotype of KRAS mutant cancer cells.Scientific reports · 2021Article
- Biological Adaptations of Tumor Cells to Radiation Therapy.Frontiers in oncology · 2021Review
- The Paradoxical Role of Cellular Senescence in Cancer.Frontiers in cell and developmental biology · 2021Review
- Modeling Resistance and Recurrence Patterns of Combined Targeted-Chemoradiotherapy Predicts Benefit of Shorter Induction Period.Cancer research · 2020Article
- Radioresistance of KRAS/TP53-mutated lung cancer can be overcome by radiation dose escalation or EGFR tyrosine kinase inhibition in vivo.International journal of cancer · 2020Article
- Activation of epidermal growth factor receptor signaling mediates cellular senescence induced by certain pro-inflammatory cytokines.Aging cell · 2020Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
The mechanisms by which inhibition of the epidermal growth factor receptor (EGFR) sensitizes non-small cell lung cancer (NSCLC) cells to ionizing radiation remain poorly understood. We set out to characterize the radiosensitizing effects of the tyrosine kinase inhibitor erlotinib and the monoclonal antibody cetuximab in NSCLC cells that contain wild-type p53. Unexpectedly, EGFR inhibition led to pronounced cellular senescence but not apoptosis of irradiated cells, both in vitro and in vivo. Senescence was completely dependent on wild-type p53 and associated with a reduction in cell number as well as impaired clonogenic radiation survival. Study of ten additional NSCLC cell lines revealed that senescence is a prominent mechanism of radiosensitization in 45% of cell lines and occurs not only in cells with wild-type p53 but also in cells with mutant p53, where it is associated with an induction of p16. Interestingly, senescence and radiosensitization were linked to an increase in residual radiation-induced DNA double-strand breaks irrespective of p53/p16 status. This effect of EGFR inhibition was at least partially mediated by disruption of the MEK-ERK pathway. Thus, our data indicate a common mechanism of radiosensitization by erlotinib or cetuximab across diverse genetic backgrounds. Our findings also suggest that assays that are able to capture the initial proliferative delay that is associated with senescence should be useful for screening large cell line panels to identify genomic biomarkers of EGFR inhibitor-mediated radiosensitization.
Indexed as
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.